Clinical Characteristics and Disease Progression Among Non-Diabetic APOL1-Mediated Kidney Disease Patients and Patients with Other CKD

Background: Apolipoprotein L1 ( APOL1 )-mediated kidney disease (AMKD) is an aggressive form of chronic kidney disease (CKD). This study described characteristics of non-diabetic patients with AMKD and compared their disease progression to non-diabetic patients with other forms of CKD. Methods: This retrospective study used clinical and biosample data from NashBio (Nashbio contains electronic health records (EHR) generated during clinical encounters at Vanderbilt University Medical Center (VUMC)). Non-diabetic patients with ≥ 1 CKD diagnosis code who were ≥10 years of age at index (date of first CKD diagnosis code in patient’s medical record) were included. The AMKD and other forms of CKD cohorts were defined based on the presence of APOL1 risk alleles and then their clinical and demographic characteristics were described. To assess progression patients were matched 1:1 on gender, presence of hypertension, and CKD stage at index and were followed until the last observation in the data. Progression outcomes including time from index to dialysis, kidney transplant, and diagnosis of CKD requiring kidney replacement therapy were assessed using Kaplan-Meier analysis, with log-rank tests used to compare matched cohorts. Results: The study included 645 patients with AMKD and 6,749 patients with other forms of CKD. AMKD patients were significantly younger than other CKD patients (median 44.0 vs. 61.0 years; p<0.001) and had significantly less comorbidity burden such as cardiovascular diseases (16.9% versus 36.6% p < 0.001). Additionally, AMKD patients had higher rates of CKD requiring kidney replacement therapy at index (59% vs. 24%, p<0.001). After 1:1 matching, AMKD patients reached dialysis and kidney transplant significantly faster than other CKD patients (both p<0.001). Among patients who did not require kidney replacement therapy at index (n=264 per cohort), AMKD patients progressed to CKD requiring kidney replacement therapy significantly faster than other CKD patients (p<0.01). Conclusions: Non-diabetic patients with AMKD experienced more rapid disease progression than patients with other forms of CKD, despite being younger and having lower comorbidity burden.